Aberrant expression of the pluripotency-associated transcription factor Sox2 is associated with poor prognosis in colorectal cancer (CRC). We investigated the regulatory roles of major post-translational modifications in Sox2 using two CRC cell lines, SW480 and SW620, derived from the same patient but with low and high Sox2 expression, respectively. Acetylation of K75 in the Sox2 nuclear export signal was relatively increased in SW480 cells and promotes Sox2 nucleocytoplasmic shuttling and proteasomal degradation of Sox2. LC-MS-based proteomics analysis identified HDAC4 and p300 as binding partners involved in the acetylation-mediated control of Sox2 expression in the nucleus. Sox2 K75 acetylation is mediated by the acetyltransferase activity of CBP/p300 and ACSS3. In SW620 cells, HDAC4 deacetylates K75 and is regulated by miR29a.O-GlcNAcylation on S246, in addition to K75 acetylation, also regulates Sox2 stability. These findings provide insights into the regulation of Sox2 through multiple post-translational modifications and pathways in CRC.
多能性相关转录因子Sox2的异常表达与结直肠癌（CRC）的不良预后相关。本研究利用源自同一患者但分别具有低表达和高表达Sox2的两种CRC细胞系SW480和SW620，探讨了主要翻译后修饰对Sox2的调控作用。在SW480细胞中，Sox2核输出信号中K75位点的乙酰化修饰相对增加，该修饰促进了Sox2的核质穿梭及其蛋白酶体降解。基于LC-MS的蛋白质组学分析鉴定出HDAC4和p300是通过乙酰化介导调控细胞核内Sox2表达的结合伴侣。Sox2 K75乙酰化由CBP/p300和ACSS3的乙酰转移酶活性介导。在SW620细胞中，HDAC4对K75进行去乙酰化，该过程受miR29a调控。除K75乙酰化外，S246位点的O-GlcNAc糖基化修饰也调控Sox2的稳定性。这些发现揭示了结直肠癌中通过多种翻译后修饰及通路调控Sox2表达的分子机制。
肿瘤(癌症)患者之家